Cell Replacement Therapy for Parkinson's Disease

How Close Are We to the Clinic?

Javier Ganz; Nirit Lev; Eldad Melamed; Daniel Offen

Disclosures

Expert Rev Neurother. 2011;11(9):1325-1339. 

In This Article

Does PD Affect the Grafts?

In order to answer this question, post-mortem studies from long-term implanted patients were needed. Indeed, reports concerning this issue have only recently emerged. Mendez et al. reported no PD pathology in a graft that survived for 14 years.[137] Several patients that were transplanted 4–9 years before their death did not contain any PD pathology in the grafted cells.[40,95] However, Li et al. reported two patients transplanted twice, who died 13–16 years after their first transplantation. They had numerous surviving DA neurons, some of whom contained α-synuclein and ubiquitin-positive Lewy bodies and neuritis.[138] In a second report, Kordower et al. described two patients that died 14 years after transplantation who showed aggregated and neurotic α-synuclein, as well as decreased staining for dopamine transporter with normal staining for TH and VMAT-2.[139] Clinically, these patients suffered from a progressive clinical deterioration from 11–12 years post-transplantation. These findings may suggest progressive graft failure after a decade with compensatory changes.[139] Li et al. recently reported on a 12-year-old graft with 1.9% of the DA neurons containing Lewy bodies and a 16-year-old graft with 5% of the cells containing Lewy bodies from two autopsies.[140]

Taken together, these are encouraging reports since they suggest that transplanted cells may integrate and function for more than a decade and most cells will still not be affected by the diseased brain in which they are implanted in. Moreover, it is yet to be explored whether DA cells from different origins are as vulnerable to the disease process as the previously reported embryonic DA neurons.

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